Microparticles (MPs) are known to be increased in various malignancies and are involved in tumor invasion, angiogenesis, coagulation, and metastasis. We investigated the plasma levels of annexin-V MPs (AV(+)MPs), platelet-derived MPs (PMPs), and endothelial-derived MPs (EMPs) in patients with melanoma (n=129) and in healthy controls (n=49). A functional coagulation test STA Procoag-PPL measuring the clotting time was performed on samples containing MPs to evaluate their procoagulant potential. The plasma levels of PMPs, EMPs, and AV(+)MPs were significantly higher, and the clotting time-PPL was significantly lower in melanoma patients than in healthy controls. The plasma levels of PMPs, EMPs, and AV(+)MPs were higher in stage IV than in the other stages of melanoma, but with no significant difference. In addition, we observed an inverse correlation between PMPs, AV(+)MPs, and clotting times. Our data suggest that MPs are involved in the progression of melanoma and may be associated to melanoma-associated thrombogenesis.
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We investigated the plasma levels of PMPs in patients with 45 stage III and 45 stage IV melanoma. PMPs were characterised by flow cytometry and their thrombogenic activity. We also investigated the link between PMPs circulating levels and tumor burden. The circulating levels of PMPs were significantly higher in stage IV (8500 μL
| BACKGROUNDMicroparticles (MPs) are membrane vesicles generated from different cellular compartments and released by any cell type into the vascular compartment during activation or apoptosis processes. In cancer, MPs are involved in metastatic progression through angiogenesis, immune escape and thrombogenicity. [1,2] We previously demonstrated [3] that the plasma levels of PMPs were significantly higher, and the clotting time-PPL was significantly lower in patients with melanoma than in healthy controls. However, MPs levels did not significantly differ between the different stages of melanoma.
| QUESTIONS ADDRESSEDPrevious data prompted us to compare the level of circulating PMPs in patients with stage III and IV melanoma as stage III patients are considered as high-risk of disease recurrence.
| EXPERIMENTAL DESIGNIn a monocentric prospective study, we investigated the plasma levels of PMPs by flow cytometry and evaluated their thrombogenic activity by measuring the clotting time (3, s4, s5
| RESULTSThere was a significant difference between the plasma levels of PMPs in patients with stage III and in stage IV melanoma (Table S1, Figures
| CONCLUSIONSAlthough PMPs level has been correlated with metastatic tumors, [2,4] the function of high PMPs levels in advanced melanoma still need to be explored. Our study demonstrates that circulating PMPs are
| LETTER TO THE EDITORsignificantly increased in patients with stage IV compared to stage III melanoma with no correlation to tumor burden. In addition, we calculated a threshold value of PMPs plasma level that differentiates stages III and IV with a high specificity and PPV. The exact mechanisms inducing platelet activation and then formation of PMPs in cancer are not well understood, but it seems that there is a direct activation by the tumoral cells releasing procoagulant molecules such as the tissue factor [2] as well as an indirect activation by immune cells. [5,6] In our study, we did not find any association between the plasma level of PMPs and tumor burden using RECIST criteria or radiographic contouring, for all sizes of PMPs in patients with stage IV melanoma. We do not have any clear explanation but we may hypothesise that PMPs reflect the tumor microenvironment, including angiogenesis, inflammatory reaction and antitumoral immunity rather than tumor burden. [5] It may also be suggested that PMPs may not be representative of tumor burden as recently suggested by Willms et al. [4] Cancer-associated venous thromboembolism constitutes the second cause of death after cancer. [7] We previously observed an inverse correlation between PMPs and clotting times with a lower clotting time in stage IV patients as compared to stage II...
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